The objective of the proposed research is to study the secretion, reuptake, and synthesis of norepinephrine (NE) in the heart of the open- chest, anesthetized dog. The overflow of NE will be determined by multiplying the coronary blood flow by the difference in concentrations of NE in coronary sinus and arterial blood. The effects of the following factors on the rate of NE overflow during cardiac sympathetic nerve stimulation will be ascertained: (a) frequency and train duration of nerve stimulation, (b) rate of coronary blood flow, (c) coronary arterial blood gas concentrations, (d) coronary arterial NE concentration and (e) concomitant vagal stimulation. The apparent depletion of the "secretory pool" of NE will also be investigated. The role of the following factors in the tendency for sympathetic nerve stimulation to lead to depletion will be studied: (a) coronary blood flow, (b) coronary arterial blood gas concentrations, (c) preceding infusion of NE, (d) inhibition of NE synthesis, and (e) administration of angiotensin. Also, the tendency for the depletion of the secretory pool of NE by reflexly induced sympathetic activity and during hemorrhagic shock will be studied, and the role of such depletion in the pathogenesis of heart failure during shock will be assessed.